Format

Send to

Choose Destination
Nat Immunol. 2019 Apr;20(4):503-513. doi: 10.1038/s41590-019-0315-3. Epub 2019 Feb 18.

Quantifying in situ adaptive immune cell cognate interactions in humans.

Author information

1
Department of Medicine, Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL, USA.
2
Department of Radiology and Committee on Medical Physics, University of Chicago, Chicago, IL, USA.
3
Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
4
Department of Pathology, University of Chicago, Chicago, IL, USA.
5
Department of Radiology and Committee on Medical Physics, University of Chicago, Chicago, IL, USA. m-giger@uchicago.edu.
6
Department of Medicine, Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL, USA. mclark@uchicago.edu.

Abstract

Two-photon excitation microscopy (TPEM) has revolutionized the understanding of adaptive immunity. However, TPEM usually requires animal models and is not amenable to the study of human disease. The recognition of antigen by T cells requires cell contact and is associated with changes in T cell shape. We postulated that by capturing these features in fixed tissue samples, we could quantify in situ adaptive immunity. Therefore, we used a deep convolutional neural network to identify fundamental distance and cell-shape features associated with cognate help (cell-distance mapping (CDM)). In mice, CDM was comparable to TPEM in discriminating cognate T cell-dendritic cell (DC) interactions from non-cognate T cell-DC interactions. In human lupus nephritis, CDM confirmed that myeloid DCs present antigen to CD4+ T cells and identified plasmacytoid DCs as an important antigen-presenting cell. These data reveal a new approach with which to study human in situ adaptive immunity broadly applicable to autoimmunity, infection, and cancer.

PMID:
30778242
PMCID:
PMC6474677
DOI:
10.1038/s41590-019-0315-3
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center